title: Case report series of left atrial thrombus formation in patients on dabigatran therapy.
abstract: Dabigatran etexilate mesylate, a direct thrombin inhibitor, has been approved in the United States as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. The authors report 2 cases of development of large left atrial thrombi and unfortunate occurrence of thromboembolic events in patients with chronic atrial fibrillation, despite these patients being compliant with recommended dabigatran therapy. The authors postulate that certain unique pharmacologic characteristics of the drug may be disadvantageous toward providing a therapeutic level of anticoagulation in all patients and may provide an explanation of occurrence of these thrombotic events, namely, (1) a competitive, reversible, and incomplete inhibition of only one coagulation factor (thrombin), as opposed to warfarin that leads to noncompetitive inhibition of multiple coagulation factors, (2) a short half-life (12-17 hours) and linear pharmacodynamics related to drug levels that conceivably causes an hourly variation of the level of anticoagulation, (3) a much lower incidence of supratherapeutic anticoagulation ("overshoot") with dabigatran as compared with warfarin, and (4) a reported increase in the coagulation factors that follows long-term use of dabigatran. Also, the absence of routine monitoring to test the therapeutic efficacy of the drug prevents diagnosis of cases where anticoagulation remains subtherapeutic. These factors could explain occurrence of the thrombotic and thromboembolic events in our cases.
authors.affiliation: 1Central Cardiology, Bakersfield, CA 2Divsion of Cardiology, Department of Medicine, Bakersfield Heart Hospital, Bakersfield, CA.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sharma
authors.forename: Sarabjeet
authors.initials: S
authors.lastname: Singh
authors.forename: Rasham
authors.initials: R
authors.lastname: Sandhu
authors.forename: Mark
authors.initials: M
authors.lastname: Monterroso
authors.forename: Neil
authors.initials: N
authors.lastname: Bhambi
authors.forename: Rohan
authors.initials: R
authors.lastname: Sharma
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000188:drug therapy; D001562:Benzimidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D000069604:Dabigatran; D016903:Drug Monitoring / Q000379:methods; D065427:Factor Xa Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced* / Q000473:pathology; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology
chemical_list: D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D011725:Pyridines; D000069604:Dabigatran